SARS-CoV-2 can spread by close contact through large droplet spray and indirect contact via contaminated objects. There is mounting evidence that it can also be transmitted by inhalation of infected ...saliva aerosol particles. These particles are generated when breathing, talking, laughing, coughing or sneezing. It can be assumed that aerosol particle concentrations should be kept low in order to minimize the potential risk of airborne virus transmission. This paper presents measurements of aerosol particle concentrations in a gym, where saliva aerosol production is pronounced. 35 test persons performed physical exercise and aerosol particle concentrations, CO2 concentrations, air temperature and relative humidity were obtained in the room of 886 m³. A separate test was used to discriminate between human endogenous and exogenous aerosol particles. Aerosol particle removal by mechanical ventilation and mobile air cleaning units was measured. The gym test showed that ventilation with air-change rate ACH = 2.2 h−1, i.e. 4.5 times the minimum of the Dutch Building Code, was insufficient to stop the significant aerosol concentration rise over 30 min. Air cleaning alone with ACH = 1.39 h−1 had a similar effect as ventilation alone. Simplified mathematical models were engaged to provide further insight into ventilation, air cleaning and deposition. It was shown that combining the above-mentioned ventilation and air cleaning can reduce aerosol particle concentrations with 80 to 90% , depending on aerosol size. This combination of existing ventilation supplemented with air cleaning is energy efficient and can also be applied for other indoor environments.
•Aerosol particle concentration measurements in a gym with 35 exercising persons.•Assessment of deposition, ventilation and air cleaning (AC) for aerosol reduction.•Gym ventilation with ACH = 2.2 h−1 has similar effect as air cleaning with ACH = 1.39 h−1.•Application of simplified mathematical models to predict other scenarios.•Combining ventilation & AC gives reduction factors 2.3 up to 3.7 depending on aerosol size.
Due to the combination of rapid influx of new technology, high pressure on time-to-market and increasing globalization, the number of products that have highly uncertain and dynamic specifications or ...customer requirements might significantly increase. In order to deal with these inherently volatile products or services, we need to adopt a more pro-active approach in order not to produce an unwanted product or service. Thus, based on the idea of the quality loss function and the zero-one goal programming, an intuitively simple mathematical model is developed to prioritize the quality characteristics (QCs) in the dynamic quality function deployment (QFD). It incorporates a pro-active approach towards providing products and services that meet the future voice of the customer (FVOC). The aim is to determine and prioritize only the 'important' QCs with a greater confidence in meeting the FVOC. It is particularly useful when the number of the potentially dominant QCs is very large so that, by using the prioritization, the size of the QFD can be effectively reduced. Some constraints, such as minimum customer satisfaction level and limitation on budget are also taken into consideration. A sensitivity analysis is suggested to give an insight to the QFD users in the change of parameters of the proposed model.
Contribution of immune mediators, interleukin-4 and interferon gamma to cognitive functioning is receiving increasing attention. However, the fundamental question about how heterodimeric ...interleukin-4 receptor alpha– and interferon gamma– producing myeloid cells converge to influence hippocampal–dependent spatial memory tasks through immunomodulation of multisensory inputs from other brain areas remains unexplored. Here, we show that mice lacking interleukin-4 receptor alpha are able to successfully learn spatial tasks, while reference memory is impaired. Moreover, the absence of interleukin-4 receptor alpha leads to simultaneous increase in proportions of CD11b + myeloid cells in the hippocampus and thalamus, but not the brainstem during acquisition. Interleukin-4 receptor alpha deletion significantly decreased expression of myeloid cell–derived interferon gamma in the thalamus during the acquisition phase and simultaneously increased brain-derived neurotrophic factor production in the thalamus and brainstem of trained mice. We provide evidence that interleukin-4 receptor alpha is essential for cognitive performance while training–induced alterations in interferon gamma activity and brain-derived neurotrophic factor signalling may contribute to neuromodulation of learned tasks and consequently affect systems–level memory encoding and consolidation.
Product reliability is often seen as a product attribute. Models with different degree of sophistication analyze and predict the reliability of a product as a function of the internal structure (such ...as components and their relation). The practical relevance of these models, in relation with the (business) processes in which the related products are actually used, is not often addressed. Different types of reliability issues, however, can be relevant for products in different industrial contexts. This paper will present a classification model to describe different business processes, based on the degree of product innovation. It will also propose a taxonomy that can be used to classify different types of reliability problems. As this paper will demonstrate, only certain combinations of reliability problems are relevant for certain business processes. It will also show that, given certain technology trends, some combinations will become more relevant in the future. The final part of this paper will demonstrate that especially for these combinations many of the existing reliability analysis and prediction methods can be considered inadequate.
In a rapidly changing environment, the priorities derived using the analytic hierarchy process (AHP) approach at one point in time might very likely change in the near future. Thus, in order to adapt ...to such ever-changing environment, it is of primary importance to be able to follow the change over time as to enable the system to respond differently and continuously over time of its operation. This paper proposes the use of a time-based compositional forecasting method, which is based on the idea of exponential smoothing, to deal with the AHP priority dynamics. The proposed method is particularly useful when there is a limited number of historical data, and might be considered to be more effective and time-efficient compared to that of multivariate time series method. It was also shown that the proposed method provides much greater adaptability in modeling the AHP priorities change over time compared to that of recently developed methods in compositional data research field. The shortcoming of Saaty’s dynamic judgment approach and some limitations of the other existing methods will be discussed. Finally, to substantiate the validity of the proposed method and to give some practical insights, an illustrative case study is provided.
Previous studies demonstrate that aluminium hydroxide adjuvant (alum) produces increased Th1 responses in IL-4-deficient mice compared with wild-type animals, although the continued production of ...IL-5 by spleen cells from these mice also indicates that Th2 responses are induced. In the present study, we demonstrate that alum can induce Th2-associated IL-4 and IL-5 production in the absence of IL-4 signaling in mice deficient in either IL-4Ralpha or Stat6. The Th2 responses observed could not be due to IL-13 as IL-13 responses are also impaired in IL-4Ralpha- and Stat6-deficient mice. We also detected higher levels of IL-4 in IL-4Ralpha gene-deficient, though not Stat6-deficient, mice compared with their wild-type counterparts. The increased levels of IL-4 could be explained by the IL-4R being unavailable to neutralize this cytokine in IL-4Ralpha-deficient mice. While levels of IL-5 production in IL-4Ralpha- or Stat6-deficient mice were similar to IL-4-deficient and wild-type mice, other type 2-associated responses, which are largely or wholly IL-4 dependent, such as the production of IgG1 or IgE Abs, were either reduced or absent. We conclude that alum adjuvants can induce IL-4 production and Th2 responses independently of IL-4 or IL-13, negating the requirement for an early source of IL-4 in the Th2 response induced by this adjuvant.
Autism spectrum disorders (ASD) are a heterogeneous group of disorders which have complex behavioural phenotypes. Although ASD is a highly heritable neuropsychiatric disorder, genetic research alone ...has not provided a profound understanding of the underlying causes. Recent developments using biochemical tools such as transcriptomics, proteomics and cellular models, will pave the way to gain new insights into the underlying pathological pathways. This review addresses the state-of-the-art in the search for molecular biomarkers for ASD. In particular, the most important findings in the biochemical field are highlighted and the need for establishing streamlined interaction between behavioural studies, genetics and proteomics is stressed. Eventually, these approaches will lead to suitable translational ASD models and, therefore, a better disease understanding which may facilitate novel drug discovery efforts in this challenging field.
Differential WNT and Notch signaling regulates differentiation of Lgr5+ crypt-based columnar cells (CBCs) into intestinal cell lineages. Recently we showed that mitochondrial activity supports CBCs, ...while adjacent Paneth cells (PCs) show reduced mitochondrial activity. This implies that CBC differentiation into PCs involves a metabolic transition toward downregulation of mitochondrial dependency. Here we show that Forkhead box O (FoxO) transcription factors and Notch signaling interact in determining CBC fate. In agreement with the organoid data, Foxo1/3/4 deletion in mouse intestine induces secretory cell differentiation. Importantly, we show that FOXO and Notch signaling converge on regulation of mitochondrial fission, which in turn provokes stem cell differentiation into goblet cells and PCs. Finally, scRNA-seq-based reconstruction of CBC differentiation trajectories supports the role of FOXO, Notch, and mitochondria in secretory differentiation. Together, this points at a new signaling-metabolic axis in CBC differentiation and highlights the importance of mitochondria in determining stem cell fate.
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•FOXO1/3 knockdown leads to stem cell differentiation into secretory cells•High and low abundance of mitochondria define stem cells and Paneth cells, respectively•FOXO and NOTCH functionally interact and their inhibition induces mitochondrial fission•Mitochondrial fission is a requisite for differentiation into Paneth and goblet cells
Changes in cellular metabolism regulate the stem cell state and differentiation. In particular, intestinal stem cells are enriched in mitochondria when compared to secretory linages. Here, Ludikhuize et al. show that downregulation of FOXO1/3 and Notch1 signaling induces mitochondrial fission, which is a requisite for the differentiation of stem cells into goblet and Paneth cells.
The vertebrate heart develops from several progenitor lineages. After early-differentiating first heart field (FHF) progenitors form the linear heart tube, late-differentiating second heart field ...(SHF) progenitors extend the atrium and ventricle, and form inflow and outflow tracts (IFT/OFT). However, the position and migration of late-differentiating progenitors during heart formation remains unclear. Here, we track zebrafish heart development using transgenics based on the cardiopharyngeal gene tbx1. Live imaging uncovers a tbx1 reporter-expressing cell sheath that continuously disseminates from the lateral plate mesoderm towards the forming heart tube. High-speed imaging and optogenetic lineage tracing corroborates that the zebrafish ventricle forms through continuous addition from the undifferentiated progenitor sheath followed by late-phase accrual of the bulbus arteriosus (BA). FGF inhibition during sheath migration reduces ventricle size and abolishes BA formation, refining the window of FGF action during OFT formation. Our findings consolidate previous end-point analyses and establish zebrafish ventricle formation as a continuous process.
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